| Description: |
Background and aims: Alcohol use behaviors (AUBs) manifest in a variety of normative and problematic ways across the life course, all of which are heritable. Twin studies show that genetic influences on AUBs change across development, but this is usually not considered in research identifying and investigating the genes linked to AUBs. Understanding the dynamics of how genes shape AUBs could point to critical periods in which interventions may be most effective and provide insight into the mechanisms behind AUB-related genes. In this project, we estimated how genetic influences on AUBs unfold across development using longitudinal modelling of polygenic scores (PGSs). Design: Using results from genome-wide association studies (GWASs), we created PGSs to index individual-level genetic risk for multiple AUB-related dimensions: Consumption, Problems, a temporally variable pattern of drinking associated with a preference for beer (BeerPref) and externalizing behavior (EXT). We created latent growth curve models and tested PGSs as predictors of latent growth factors (intercept, slope, quadratic) underlying trajectories of AUBs. Setting: PGSs were derived in six longitudinal epidemiological cohorts from the United States, United Kingdom and Finland. Participants: Participant data were obtained from the longitudinal studies AddHealth, ALSPAC, COGA, FinnTwin12, the older Finnish Twin Cohort and Spit for Science (total n = 19 194). These cohorts included individuals aged 14 to 67, with repeated measures collected over a span of 4 to 36 years. Measurements: Primary measures included monthly frequency of typical alcohol consumption (CON) and heavy episodic drinking (HED). Findings: When drinking behaviors were averaged across time, higher Consumption, Problems and EXT PGSs were robustly associated with higher levels of CON and HED (beta s ranged from 0.105 to 0.333, P < 3.09E-04) and higher BeerPref PGSs with higher HED (beta = 0.064, P = 3.65E-05). However, these PGSs were largely not associated with drinking ... |
| Relation: |
This research was funded by a grant from The Netherlands Organization for Scientific Research, VI.VENI.201G-064 to J.E.S; United States (US) National Institute on Drug Abuse (NIDA), grant T32DA55569; National Institute on Aging cooperative agreements U01AG071448 (Hummer) and U01AG071450 (Aiello and Hummer) at the University of North Carolina at Chapel Hill; the Add Health Program Project, grant P01HD31921 (Harris) from Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), with cooperative funding from 23 other federal agencies and foundations; United Kingdom (UK) Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC; National Institutes of Health, grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the NIDA support COGA; FinnTwin cohorts are supported by the NIAAA (award numbers R01AA015416, R01AA09203, K02AA018755 and K01AA024152); Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146; Wellcome Trust Sanger Institute, the Broad Institute, ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413 and the Academy of Finland Center of Excellence in Complex Disease Genetics (grant 352792); Spit for Science has been supported by Virginia Commonwealth University, P20AA017828, R37AA011408, K02AA018755, P50AA022537 and K01AA024152 from the NIAAA, UL1RR031990 from the National Center for Research Resources and National Institutes of Health Roadmap for Medical Research, as well as support by the Center for the Study of Tobacco Products at VCU; REDCap support provided by CTSA award UM1TR004360 from the National Center for Advancing Translational Sciences; the Externalizing Consortium has been supported by the NIAAA (R01AA015416-administrative supplement to D.M.D.), and the NIDA (R01DA050721 to D.M.D.); additional funding for investigator effort has been provided by K02AA018755, U10AA008401 and P50AA022537 to D.M.D., as well as a European Research Council Consolidator Grant (647648 EdGe to Koellinger).; Savage, J E, Aliev, F, Barr, P B, Choi, M, Drouard, G, Cooke, M E, Kuo, S I, Stephenson, M, Brislin, S J, Neale, Z E, Latvala, A, Rose, R J, Kaprio, J, Dick, D M, Meyers, J, Salvatore, J E & Posthuma, D 2025, 'Trajectories of genetic risk across dimensions of alcohol use behaviors', Addiction. https://doi.org/10.1111/add.70292; https://hdl.handle.net/10138/626564; 105027258676; 001647903600001 |